Summary: Clinical trials using porcine tissues or cells are underway. Since all pigs carry in their genome porcine endogenous retroviruses (PERV), these xenotransplantation procedures carry the risk of exposure to and transmission of PERV. We previously showed that activation of PERV occurs after exposure of pig primary peripheral blood mononuclear cells (PBMC) to mitogenic agents. We now have shown that porcine plasma also carries infectious PERV that was isolated from plasma four out of four NIH mini pigs. We then extended this analysis to a licensed biologic derived from porcine plasma, Hyate:C (porcine factor VIII). Clinical lots of Hyate:C were positive for PERV RNA sequences and for a viral enzyme. However, infectivity assays performed on six lots of Hyate:C failed to detect infectious PERV, demonstrating that the clinical material only retained fragments of inactivated virus. The results from these studies highlight two important points: 1) isolation of infectious PERV from plasma confirms that PERV is expressed in vivo in some pig compartments, highlighting the potential for exposure to PERV in porcine xenotransplantation recipients; 2)the analysis of Hyate:C underscores the need for incorporating robust viral inactivation and removal methods in the manufacture of products derived from animal sources.